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Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply

We would like to reply to the letter by Dolff and colleagues [1] regarding our article in a recent issue of Arthritis Research & Therapy [2]. We thank the authors for their interest in our work and the critical reading of our article. The aim of our study was to investigate a possible association between the IFN type I signature and memory T helper 17 (Th17) cells and their cytokines in systemic lupus erythematosus (SLE). Since CCR6 can be expressed by regulatory T (Treg) cells, we have excluded CD25high cells to discriminate between CD4+CD45RO+CCR6+CD25 (primary Th17 cells) and Treg cells. Concerning the observation on co-expression of IL-17A with IFN-γ, we would like to remark that IFN-γ is an IFN type II, and not an IFN type I, cytokine and does not bind to the IFN type I receptor. Detection of IFN type I activity is hampered by the difficulty to assess the different subtypes of this cytokine. Therefore, analysis of IFN type I-induced gene expression in RNA from peripheral blood cells, the so-called IFN type I signature, is used as a measure for IFN type I activity. Although we fully agree with the authors that the relationship between Th cells and IFN type I deserves further study, their remark on the ‘genetic’ signature is confusing and probably refers to the IFN type I-induced gene expression signature, which is detected at the RNA level.

The relationship between CD25+ Tregs and IFN type I is certainly of interest for further study as these Tregs are carrying the IFN type I receptor and thus respond to increased systemic IFN type I activity in SLE. Also, follow-up studies with a focus on adaptive and innate cells producing IL-17, including the relation with IL-21 and IL-22 and plasticity, will be of interest [3, 4]. In our article, we presented data supporting a potential co-activity between IFN type I and CD4+memory CCR6+ Th17 cytokines. Further studies are needed to confirm this co-activity with a focus on revealing the mechanism of this dangerous link in SLE.







Systemic lupus erythematosus


T helper 17


Regulatory T.


  1. Dolff S, Abdulahad WH, Kallenberg CGM: Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’. Arthritis Res Ther. 2014, 16: 409-10.1186/ar4576.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Brkic Z, Corneth OB, van Helden-Meeuwsen CG, Dolhain RJ, Maria NI, Paulissen SM, Davelaar N, van Hamburg JP, van Daele PL, Dalm VA, van Hagen PM, Hazes JM, Versnel MA, Lubberts E: T helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?. Arthritis Res Ther. 2014, 16: R62-10.1186/ar4499.

    Article  PubMed Central  PubMed  Google Scholar 

  3. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G: Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007, 8: 639-646. 10.1038/ni1467.

    Article  CAS  PubMed  Google Scholar 

  4. Hirota K, Duarte JH, Veldhoen M, Hornsby E, Li Y, Cua DJ, Ahlfors H, Wilhelm C, Tolaini M, Menzel U, Garefalaki A, Potocnik AJ, Stockinger B: Fate mapping of IL-17-producing T cells in inflammatory responses. Nat Immunol. 2011, 12: 255-263. 10.1038/ni.1993.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Correspondence to Erik Lubberts.

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The authors declare that they have no competing interests.

Marjan A Versnel and Erik Lubberts contributed equally to this work.

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Brkic, Z., Corneth, O.B., Versnel, M.A. et al. Response to ‘T-helper 17 cell cytokines and interferon type I: partners in crime in systemic lupus erythematosus?’ – Authors’ reply. Arthritis Res Ther 16, 410 (2014).

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  • Systemic Lupus Erythematosus
  • Interferon
  • Th17 Cell
  • Treg Cell
  • Expression Signature